Fungi are ubiquitous pathogenic organisms which can cause opportunistic infections in humans and other mammals. Some of these infections, although generally not life threatening, are widespread among the general population, occurring in individuals that are otherwise in good health. Vaginitis, caused by Candida species, is one of the more common examples. In recent years, there has been an increase in infections caused by Candida and other fungal pathogens, especially those which have serious and even life threatening health implications. Such infections generally occur in patients with compromised immune systems, such as patients undergoing chemotherapy or corticosteroid treatments. This recent rise in life threatening fungal infections is largely a result of an increase in the number of transplants and the accompanying immunosuppressive therapies and of the spread of AIDS.
Unfortunately, there are few drugs available today for the treatment of fungal infections. Those that are available have serious shortcomings. They have a limited spectrum of activity, and many are toxic or are no longer effective because the target organism has become resistant. For example, pulmonary and disseminated infections caused by Aspergillus fumigatus in neutropenic or immunosuppressed patients are often fatal because treatments, such as the administration of Amphotericin B, are ineffective. Amphotericin B is also used for infections caused by Candida species, Cryptococcus neoformans, Blastomyces dermatidis, Coccodioides immitis, and Histoplasma capsultatum and has many undesirable side effects. Azoles, a class of antifungal agents (e.g. Fluconazole, used against Candida and Cryptococcus nerformans infections) can be effective, but are active against a limited range of fungi and resistant strains have emerged. Pneumocystis carinii is responsible for the most common opportunistic infection (pneumocystis pneumonia) in AIDS patients, in whom the infection is often fatal. Treatment with drugs such as trimethoprim-sulfamethoxazole and dapsone is often ineffective and may be limited by the drugs' toxicity.
Consequently, there exists a need for developing new therapies for treating infections by fungal pathogens. As an aid in developing new therapies, it would be of great value to have an assay which could rapidly detect new compounds which can interrupt a cellular process essential for growth or virulence of the fungi, and, thus, act as antifungal agents.